We have studied in culture vascular smooth muscle cells (VSMC) obtained from either spontaneously hypertensive rats (SHR) or Wistar-Kyoto rats (WKR). VSMC from SHR proliferated more rapidly than cells from WKR regardless of the medium used. The incorporation of radioactive thymidine into DNA was also greater in SHR VSMC than for cells from WKR. To determine if this increased growth was due to the production of growth factors, medium was taken from the cells and incubated with quiescent SHR or WKR VSMC for 24 hours. However, none of the media tested would promote DNA synthesis in either type of cells with or without added 1% fetal bovine serum (FBS). Thus the increased growth response was not due to the production of growth factors by the cells. Platelet derived growth factor (PDGF) did not promote DNA synthesis in these cells. However, both epidermal growth factor (EGF) and fibroblast growth factor (FGF) stimulated DNA synthesis of both SHR and WKY, but in each case, produced greater stimulation in SHR than in WKR VSMC. Of the growth factors tested, EGF produced the greatest response and its effects were either additive or synergistic when it was added to either FGF or PDGF. Specific ligand binding studies of 125-I-EGF to quiescent VSMC showed that the VSMC from SHR had both a greater affinity and a greater number of binding sites for EGF than did the cells from WKR.